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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q7KZI7: Variant p.Phe194Ser

Serine/threonine-protein kinase MARK2
Gene: MARK2
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Variant information Variant position: help 194 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Phenylalanine (F) to Serine (S) at position 194 (F194S, p.Phe194Ser). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from large size and aromatic (F) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In MRD76; likely pathogenic. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 194 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 788 The length of the canonical sequence.
Location on the sequence: help RDLKAENLLLDADMNIKIAD F GFSNEFTFGNKLDTFCGSPP The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         RDLKAENLLLDADMNIKIADFGFSNEFTFGNKLDTFCGSPP

Mouse                         RDLKAENLLLDADMNIKIADFGFSNEFTFGNKLDTFCGSPP

Rat                           RDLKAENLLLDADMNIKIADFGFSNEFTFGNKLDTFCGSPP
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 788 Serine/threonine-protein kinase MARK2
Domain 53 – 304 Protein kinase
Active site 175 – 175 Proton acceptor
Modified residue 208 – 208 Phosphothreonine; by LKB1 and TAOK1
Modified residue 212 – 212 Phosphoserine; by GSK3-beta
Mutagenesis 208 – 208 T -> A. Prevents phosphorylation and activation by STK11/LKB1 complex.



Literature citations
MARK2 variants cause autism spectrum disorder via the downregulation of WNT/beta-catenin signaling pathway.
Gong M.; Li J.; Qin Z.; Machado Bressan Wilke M.V.; Liu Y.; Li Q.; Liu H.; Liang C.; Morales-Rosado J.A.; Cohen A.S.A.; Hughes S.S.; Sullivan B.R.; Waddell V.; van den Boogaard M.H.; van Jaarsveld R.H.; van Binsbergen E.; van Gassen K.L.; Wang T.; Hiatt S.M.; Amaral M.D.; Kelley W.V.; Zhao J.; Feng W.; Ren C.; Yu Y.; Boczek N.J.; Ferber M.J.; Lahner C.; Elliott S.; Ruan Y.; Mignot C.; Keren B.; Xie H.; Wang X.; Popp B.; Zweier C.; Piard J.; Coubes C.; Mau-Them F.T.; Safraou H.; Innes A.M.; Gauthier J.; Michaud J.L.; Koboldt D.C.; Sylvie O.; Willems M.; Tan W.H.; Cogne B.; Rieubland C.; Braun D.; McLean S.D.; Platzer K.; Zacher P.; Oppermann H.; Evenepoel L.; Blanc P.; El Khattabi L.; Haque N.; Dsouza N.R.; Zimmermann M.T.; Urrutia R.; Klee E.W.; Shen Y.; Du H.; Rappaport L.; Liu C.M.; Chen X.;
Am. J. Hum. Genet. 111:2392-2410(2024)
Cited for: VARIANTS MRD76 71-ARG--LEU-788 DEL; VAL-80; ARG-135; SER-194; 253-GLN--LEU-788 DEL; 302-ARG--LEU-788 DEL; GLN-302; 584-ARG--LEU-788 DEL; 664-ARG--LEU-788 DEL; 747-GLN--LEU-788 DEL; ALA-752 AND PRO-764; INVOLVEMENT IN MRD76;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.